The general goal of our investigations is to define and characterize decline in immunity which accompanies thymic involution and aging. During the previous year, we have used dietary manipulation, low-dose irradiation, thymectomy, and cellular reconstitution in mouse strains with high tumor incidence, autoimmune disease or unusual longevity to study natural and artificially created T-helper or T-suppressor cell imbalance. The mutant obese diabetic mouse has been studied in relation to its specific decline of in vivo, but not in vitro, immune cell function. Selective, strain-dependent T-cell subpopulation decline may be correlated with a variety of disease states encountered in the aging host. We propose to continue experiments designed to elucidate the nature of cellular imbalance, and to explore manipulative treatments which may prolong normal immune function in the aging host.